Synthetic peptides corresponding to human follicle-stimulating hormone (hFSH)-beta-(1-15) and hFSH-beta-(51-65) induce uptake of 45Ca++ by liposomes: evidence for calcium-conducting transmembrane channel formation

Endocrinology. 1991 Jun;128(6):2745-51. doi: 10.1210/endo-128-6-2745.

Abstract

We have previously described FSH receptor-mediated influx of 45Ca++ in cultured Sertoli cells from immature rats and receptor-enriched proteoliposomes via activation of voltage-sensitive and voltage-independent calcium channels. We have further shown that this effect of FSH does not require cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding protein or activation of adenylate cyclase. In the present study, we have identified regions of human FSH-beta-subunit which appear to be involved in mediating calcium influx. We screened 11 overlapping peptide amides representing the entire primary structure of hFSH-beta-subunit for their effects on 45Ca++ flux in FSH receptor-enriched proteoliposomes. hFSH-beta-(1-15) and hFSH-beta-(51-65) induced uptake of 45Ca++ in a concentration-related manner. This effect of hFSH-beta-(1-15) and hFSH-beta-(51-65) was also observed in liposomes lacking incorporated FSH receptor, suggesting that the peptide amides may act as ionophores or channel-formers. Reducing membrane fluidity by incubating liposomes (containing no receptor) with hFSH-beta-(1-15) or hFSH-beta-(51-65) at temperatures lower than the transition temperatures of their constituent phospholipids resulted in no significant (P greater than 0.05) difference in 45Ca++ uptake. The effectiveness of the calcium ionophore A23187, however, was abolished. Ruthenium red, a voltage-independent calcium channel antagonist, was able to completely block uptake of 45Ca++ induced by hFSH-beta-(1-15) and hFSH-beta-(51-65) whereas nifedipine, a calcium channel blocker specific for L-type voltage-sensitive calcium channels, was without effect. These results suggest that in addition to its effect on voltage-sensitive calcium channel activity, interaction of FSH with its receptor may induce formation of transmembrane aqueous channels which also facilitate influx of extracellular calcium.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amides / pharmacology
  • Calcium / pharmacokinetics*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / metabolism
  • Calcium Radioisotopes
  • Follicle Stimulating Hormone / chemical synthesis
  • Follicle Stimulating Hormone / pharmacology*
  • Follicle Stimulating Hormone, beta Subunit*
  • Humans
  • Liposomes / metabolism*
  • Membrane Fluidity
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / pharmacology*
  • Phosphatidylcholines / chemical synthesis
  • Phosphatidylcholines / pharmacology*

Substances

  • Amides
  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Radioisotopes
  • Follicle Stimulating Hormone, beta Subunit
  • Liposomes
  • Peptide Fragments
  • Phosphatidylcholines
  • follicle stimulating hormone, beta subunit (51-65)
  • follicle stimulating hormone, beta subunit (1-15)
  • 1-palmitoyl-2-parinaroylphosphatidylcholine
  • Follicle Stimulating Hormone
  • Calcium